scholarly journals Therapeutic Hypothermia for Acute Ischemic Stroke: Ready to Start Large Randomized Trials?

2010 ◽  
Vol 30 (6) ◽  
pp. 1079-1093 ◽  
Author(s):  
H Bart van der Worp ◽  
Malcolm R Macleod ◽  
Rainer Kollmar ◽  

Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.

2019 ◽  
Vol 40 (3) ◽  
pp. 461-481 ◽  
Author(s):  
Longfei Wu ◽  
Di Wu ◽  
Tuo Yang ◽  
Jin Xu ◽  
Jian Chen ◽  
...  

Acute ischemic stroke is a leading cause of death and disability worldwide. Therapeutic hypothermia has long been considered as one of the most robust neuroprotective strategies. Although the neuroprotective effects of hypothermia have only been confirmed in patients with global cerebral ischemia after cardiac arrest and in neonatal hypoxic ischemic encephalopathy, establishing standardized protocols and strictly controlling the key parameters may extend its application in other brain injuries, such as acute ischemic stroke. In this review, we discuss the potential neuroprotective effects of hypothermia, its drawbacks evidenced in previous studies, and its potential clinical application for acute ischemic stroke especially in the era of reperfusion. Based on the different conditions between bench and bedside settings, we demonstrate the importance of vascular recanalization for neuroprotection of hypothermia by analyzing numerous literatures regarding hypothermia in focal cerebral ischemia. Then, we make a thorough analysis of key parameters of hypothermia and introduce novel hypothermic therapies. We advocate in favor of the process of clinical translation of intra-arterial selective cooling infusion in the era of reperfusion and provide insights into the prospects of hypothermia in acute ischemic stroke.


2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.


2016 ◽  
Vol 27 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Jingrui Pan ◽  
Xiangpen Li ◽  
Ying Peng

AbstractStroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future.


Stroke ◽  
2008 ◽  
Vol 39 (1) ◽  
pp. 87-99 ◽  
Author(s):  
Harold P. Adams ◽  
Mark B. Effron ◽  
James Torner ◽  
Antoni Dávalos ◽  
Judith Frayne ◽  
...  

2020 ◽  
Vol 17 (2) ◽  
pp. 1147-1167
Author(s):  
Yannick Lutz ◽  
◽  
Rosa Daschner ◽  
Lorena Krames ◽  
Axel Loewe ◽  
...  

2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Amrou Sarraj ◽  
Sheryl Martin-Schild ◽  
Amelia K Boehme ◽  
Emilio P Supsupin ◽  
Clark W Sitton ◽  
...  

Background: Intra-arterial therapy (IAT) is an approach to promote recanalization in acute ischemic stroke (AIS) patients. While IAT continues to go through further evaluation in multiple phase III trials using new devices and focusing on time improvement, patients with LAO continue to be treated with IAT. Multiple clinical, radiographic and time factors go into vascular neurologists’ decisions whether to pursue IAT or not. We aimed to evaluate factors affecting determination of IAT for stroke amongst patients transferred to tertiary centers. Methods: A US multicenter retrospective cohort analysis was conducted on 313 consecutive transferred patients who met vessel criteria from 01/08-4/14. Collateral were measured by the collateral score (CS). ASPECTS decay was defined as a change from good (8-10) to poor (0-7) scores between center CT scans. IAT patients were compared with no IAT patients with regard to factors predictive of IAT. Results: Table 1 shows baseline characteristics of the two groups. Age was not a predictor of IAT. NIHSS was associated with IAT, but was not a predictor of IAT. For each escalating point on CS, the odds of IAT increased more than 4 times (OR 4.27, 95% CI 2.86-7.87, p<0.0001). For each declining point on ASPECTS, the odds of IAT decreased by 22% (OR 0.78, 95% CI 0.72-0.85, p<0.0001). ASPECTS decay was associated with an 83% reduction in the odds of IAT (OR 0.17, 95% CI 0.05-0.52, p<0.0001). For every 30 minutes of time between centers, the odds of ASPECTS decay increased by 13% (OR 1.13, 95% CI 1.11-1.17 p=0.0004) and IAT chances reduced by 9% (OR 0.91, 95% CI 0.84-1.00, p=0.05). Conclusions: Infarction evolution measured by ASPECTS decay, collaterals status and time from stroke ictus are all major determinants of the vascular neurologist decision whether to proceed with IAT. Our findings further support the time-sensitivity of the process for transferring candidates for IAT.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jie Xu ◽  
Yongjun Wang

Background and Aims: Evidenced by TASTE phase III trial, 90-day good functional outcomes favored the edaravone dexborneol group versus edaravone group when administered within 48 hours after Acute Ischemic Stroke (AIS). The present study aimed to investigate the effects of edaravone dexborneol versus edaravone in AIS patients with hypertension medical history. Methods: This study was a subgroup analysis of the TASTE trial with hypertension medical history. The primary outcome was the proportion of patients with modified Rankin Scale (mRS) score ≤1 on day 90 after randomization. The secondary outcome was the mRS score on day 90. The safety endpoints were the incidences of adverse events, serious adverse events and deaths. Analyses were by intention to treat. Results: We included 767 AIS patients with hypertension (390 in edaravone dexborneol group, 377 in edaravone group) in this analysis. Among them, 252 (64.62%) in edaravone dexborneol group versus 199 (52.79%) in edaravone group reached mRS score ≤1 on D90, revealing significantly higher proportion of mRS score ≤1 on D90 in edaravone dexborneol group (OR 1.63 [95% CI, 1.22-2.18]; P<0.001). Significant differences occurred between two groups in mRS score on D90 ([OR 1.32 [95% CI, 1.02-1.72]; P=0.038). The safety outcomes indicated that the two groups were similar in incidences of adverse events (366 [93.85%] versus 352 [93.37%], p=0.787), serious adverse events (48 [12.31%] versus 34 [9.02%], p=0.1405) and number of deaths (6 [1.54%] versus 4 [1.06%], p=0.56). Conclusion: This analysis demonstrated that AIS patients with hypertension receiving edaravone dexborneol had better functional outcomes than those with edaravone, which provided evidences for the clinical application of edaravone dexborneol in AIS patients with hypertension. Keywords: Edaravone dexborneol, Acute ischemic stroke, Hypertension, mRS score


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